Amyloid precursor protein induces reactive astrogliosis

J 2024

Amyloid precursor protein induces reactive astrogliosis

JAUREGUI, Gretsen Velezmoro; Dragana VUKIĆ; Isaac G ONYANGO; Carlos ARIAS; Jan S NOVOTNY et. al.

Základní údaje

Originální název

Amyloid precursor protein induces reactive astrogliosis

Autoři

JAUREGUI, Gretsen Velezmoro; Dragana VUKIĆ (688 Srbsko, domácí); Isaac G ONYANGO; Carlos ARIAS; Jan S NOVOTNY; Katerina TEXLOVA; Shanshan WANG; Kristina Locker KOVACOVICOVA; Natalie POLAKOVA; Jana ZELINKOVA; Maria CARNA; Valentina LACOVICH STRAŠIL (705 Slovinsko, domácí); Brian P HEAD; Daniel HAVAS; Martin MISTRIK; Robert ZOREC; Alexei VERKHRATSKY; Liam KEEGAN (372 Irsko, domácí); Mary Anne O'CONNELL (372 Irsko, domácí); Robert RISSMAN a Gorazd B STOKIN (garant)

Vydání

Acta Physiologica, Hoboken, Wiley, 2024, 1748-1708

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.600 v roce 2023

Kód RIV

RIV/00216224:14740/24:00137238

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1111/apha.14142

UT WoS

001198119900001

EID Scopus

2-s2.0-85189957204

Klíčová slova anglicky

amyloid precursor protein; astrocytes; interferon pathway; lipopolysaccharide; reactive astrogliosis; traumatic brain injury

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 6. 2025 15:40, Mgr. Eva Dubská

Anotace

V originále

AimAstrocytes respond to stressors by acquiring a reactive state characterized by changes in their morphology and function. Molecules underlying reactive astrogliosis, however, remain largely unknown. Given that several studies observed increase in the Amyloid Precursor Protein (APP) in reactive astrocytes, we here test whether APP plays a role in reactive astrogliosis.MethodsWe investigated whether APP instigates reactive astroglios by examining in vitro and in vivo the morphology and function of naive and APP-deficient astrocytes in response to APP and well-established stressors.ResultsOverexpression of APP in cultured astrocytes led to remodeling of the intermediate filament network, enhancement of cytokine production, and activation of cellular programs centered around the interferon (IFN) pathway, all signs of reactive astrogliosis. Conversely, APP deletion abrogated remodeling of the intermediate filament network and blunted expression of IFN-stimulated gene products in response to lipopolysaccharide. Following traumatic brain injury (TBI), mouse reactive astrocytes also exhibited an association between APP and IFN, while APP deletion curbed the increase in glial fibrillary acidic protein observed canonically in astrocytes in response to TBI.ConclusionsThe APP thus represents a candidate molecular inducer and regulator of reactive astrogliosis. This finding has implications for understanding pathophysiology of neurodegenerative and other diseases of the nervous system characterized by reactive astrogliosis and opens potential new therapeutic avenues targeting APP and its pathways to modulate reactive astrogliosis.

Návaznosti

GA20-11101S, projekt VaV

Název: Objasnění úlohy RNA-editačního enzymu ADAR1 v nových biologických drahách a určení jeho postranslační regulace.

Investor: Grantová agentura ČR, Elucidating the role of the RNA editing enzyme ADAR1 in novel biological pathways and determine its posttranslational regulation.

GX21-27329X, projekt VaV

Název: ADAR-dependentní RNA editace; Jak imunitní systém a mozek porušují Centrální Dogma.

Investor: Grantová agentura ČR, ADAR RNA editing, how immune systems and brains breach The Central Dogma

LX22NPO5107, projekt VaV

Název: Národní ústav pro neurologický výzkum

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro neurologický výzkum, 5.1 EXCELES

Přiložené soubory

Amyloid_precursor_protein_induces_reactive_astrogliosis_bfkpdcdu.pdf

Citovat

JAUREGUI, Gretsen Velezmoro; Dragana VUKIĆ; Isaac G ONYANGO; Carlos ARIAS; Jan S NOVOTNY; Katerina TEXLOVA; Shanshan WANG; Kristina Locker KOVACOVICOVA; Natalie POLAKOVA; Jana ZELINKOVA; Maria CARNA; Valentina LACOVICH STRAŠIL; Brian P HEAD; Daniel HAVAS; Martin MISTRIK; Robert ZOREC; Alexei VERKHRATSKY; Liam KEEGAN; Mary Anne O'CONNELL; Robert RISSMAN a Gorazd B STOKIN. Amyloid precursor protein induces reactive astrogliosis. Acta Physiologica. Hoboken: Wiley, 2024, roč. 240, č. 6, s. 1-17. ISSN 1748-1708. Dostupné z: https://dx.doi.org/10.1111/apha.14142.

@article{2438997,
   author = {Jauregui, Gretsen Velezmoro and Vukić, Dragana and Onyango, Isaac G and Arias, Carlos and Novotny, Jan S and Texlova, Katerina and Wang, Shanshan and Kovacovicova, Kristina Locker and Polakova, Natalie and Zelinkova, Jana and Carna, Maria and Lacovich Strašil, Valentina and Head, Brian P and Havas, Daniel and Mistrik, Martin and Zorec, Robert and Verkhratsky, Alexei and Keegan, Liam and O'Connell, Mary Anne and Rissman, Robert and Stokin, Gorazd B},
   article_location = {Hoboken},
   article_number = {6},
   doi = {http://dx.doi.org/10.1111/apha.14142},
   keywords = {amyloid precursor protein; astrocytes; interferon pathway; lipopolysaccharide; reactive astrogliosis; traumatic brain injury},
   language = {eng},
   issn = {1748-1708},
   journal = {Acta Physiologica},
   title = {Amyloid precursor protein induces reactive astrogliosis},
   url = {https://onlinelibrary.wiley.com/doi/10.1111/apha.14142},
   volume = {240},
   year = {2024}
}

TY  - JOUR
ID  - 2438997
AU  - Jauregui, Gretsen Velezmoro - Vukić, Dragana - Onyango, Isaac G - Arias, Carlos - Novotny, Jan S - Texlova, Katerina - Wang, Shanshan - Kovacovicova, Kristina Locker - Polakova, Natalie - Zelinkova, Jana - Carna, Maria - Lacovich Strašil, Valentina - Head, Brian P - Havas, Daniel - Mistrik, Martin - Zorec, Robert - Verkhratsky, Alexei - Keegan, Liam - O'Connell, Mary Anne - Rissman, Robert - Stokin, Gorazd B
PY  - 2024
TI  - Amyloid precursor protein induces reactive astrogliosis
JF  - Acta Physiologica
VL  - 240
IS  - 6
SP  - 1-17
EP  - 1-17
PB  - Wiley
SN  - 17481708
KW  - amyloid precursor protein
KW  - astrocytes
KW  - interferon pathway
KW  - lipopolysaccharide
KW  - reactive astrogliosis
KW  - traumatic brain injury
UR  - https://onlinelibrary.wiley.com/doi/10.1111/apha.14142
N2  - AimAstrocytes respond to stressors by acquiring a reactive state characterized by changes in their morphology and function. Molecules underlying reactive astrogliosis, however, remain largely unknown. Given that several studies observed increase in the Amyloid Precursor Protein (APP) in reactive astrocytes, we here test whether APP plays a role in reactive astrogliosis.MethodsWe investigated whether APP instigates reactive astroglios by examining in vitro and in vivo the morphology and function of naive and APP-deficient astrocytes in response to APP and well-established stressors.ResultsOverexpression of APP in cultured astrocytes led to remodeling of the intermediate filament network, enhancement of cytokine production, and activation of cellular programs centered around the interferon (IFN) pathway, all signs of reactive astrogliosis. Conversely, APP deletion abrogated remodeling of the intermediate filament network and blunted expression of IFN-stimulated gene products in response to lipopolysaccharide. Following traumatic brain injury (TBI), mouse reactive astrocytes also exhibited an association between APP and IFN, while APP deletion curbed the increase in glial fibrillary acidic protein observed canonically in astrocytes in response to TBI.ConclusionsThe APP thus represents a candidate molecular inducer and regulator of reactive astrogliosis. This finding has implications for understanding pathophysiology of neurodegenerative and other diseases of the nervous system characterized by reactive astrogliosis and opens potential new therapeutic avenues targeting APP and its pathways to modulate reactive astrogliosis.
ER  -

JAUREGUI, Gretsen Velezmoro; Dragana VUKI$\backslash$'C; Isaac G ONYANGO; Carlos ARIAS; Jan S NOVOTNY; Katerina TEXLOVA; Shanshan WANG; Kristina Locker KOVACOVICOVA; Natalie POLAKOVA; Jana ZELINKOVA; Maria CARNA; Valentina LACOVICH STRAŠIL; Brian P HEAD; Daniel HAVAS; Martin MISTRIK; Robert ZOREC; Alexei VERKHRATSKY; Liam KEEGAN; Mary Anne O'CONNELL; Robert RISSMAN a Gorazd B STOKIN. Amyloid precursor protein induces reactive astrogliosis. \textit{Acta Physiologica}. Hoboken: Wiley, 2024, roč.~240, č.~6, s.~1-17. ISSN~1748-1708. Dostupné z: https://dx.doi.org/10.1111/apha.14142.

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